Lung-targeted polyzwitterionic lipid nanoparticles for effective treatment of lung inflammation  

作　　者：Wen Zhang Jiaxin Li Nan Wang Muzi Li Chen Peng Xinyue Zhang Guanghui Ouyang Yan Li 

机构地区：[1]Beijing Key Laboratory for Bioengineering and Sensing Technology,School of Chemistry and Biological Engineering,University of Science and Technology Beijing,Beijing 100083,China [2]CAS Key Laboratory of Colloid,Interface and Chemical Thermodynamics,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China

出　　处：《Science China Chemistry》2025年第3期1107-1116,共10页中国科学(化学英文版)

基　　金：financially supported by the National Natural Science Foundation of China (32071391);the Beijing Nova Program (20230484423);the Fundamental Research Funds for the Central Universities (06500230,FRF-BR-23-02B)。

摘　　要：Lipid nanoparticles(LNPs)are non-viral nucleic acid delivery systems that show great potential in vaccine development and disease treatment.Although LNPs are particularly advantageous for in vivo delivery,the wide application of LNPs is impeded as their systemic delivery of nucleic acid drugs to extrahepatic tissues remains highly challenging.To address this issue,we developed lung-targeted polyzwitterionic LNPs with zwitterionic polymer poly(2-methyacryloyloxyethyl phosphorylcholine)(PMPC)modified 1,2-dimyristoyl-sn-glycerol lipid for the delivery of small interfering RNA(si RNA).Three libraries with 90 PMPC-LNPs@siRNA were established.The polyzwitterionic PMPC-LNPs had high siRNA encapsulation efficiency of about 90%.The findings revealed that polyzwitterionic PMPC-LNPs@siRNA absorbed protein corona with the main component of Vitronectin,mediating lung-targeted delivery of siRNA.With good cellular uptake and endo/lysosomal escape ability,in vitro and in vivo studies demonstrated that polyzwitterionic PMPC-LNPs with siRNA against tumor necrosis factor-α(TNF-α)could significantly down-regulate the TNF-αin mRNA and protein levels,and improved the pathological features of lung inflammation.Polyzwitterionic PMPC-LNPs@siRNA achieved safe and efficient treatment of lung inflammation.Therefore,this work offered a promising siRNA therapeutic approach for lung diseases.

关 键 词：lipid nanoparticles lung inflammation small interfering RNA zwitterionic polymer protein corona 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]